Pleiotropic effects of extracellular vesicles from induced pluripotent stem cell-derived cardiomyocytes on ischemic cardiomyopathy: A preclinical study.
J Heart Lung Transplant
; 43(1): 85-99, 2024 01.
Article
em En
| MEDLINE
| ID: mdl-37611882
ABSTRACT
BACKGROUND:
Stem cell-secreted extracellular vesicles (EVs) play essential roles in intercellular communication and restore cardiac function in animal models of ischemic heart disease. However, few studies have used EVs derived from clinical-grade stem cells and their derivatives with stable quality. Moreover, there is little information on the mechanism and time course of the multifactorial effect of EV therapy from the acute to the chronic phase, the affected cells, and whether the effects are direct or indirect.METHODS:
Induced pluripotent stem cell-derived cardiomyocytes (iPSCM) were produced using a clinical-grade differentiation induction system. EVs were isolated from the conditioned medium by ultracentrifugation and characterized in silico, in vitro, and in vivo. A rat model of myocardial infarction was established by left anterior descending artery ligation and treated with iPSCM-derived EVs.RESULTS:
iPSCM-derived EVs contained microRNAs and proteins associated with angiogenesis, antifibrosis, promotion of M2 macrophage polarization, cell proliferation, and antiapoptosis. iPSCM-derived EV treatment improved left ventricular function and reduced mortality in the rat model by improving vascularization and suppressing fibrosis and chronic inflammation in the heart. EVs were uptaken by cardiomyocytes, endothelial cells, fibroblasts, and macrophages in the cardiac tissues. The pleiotropic effects occurred due to the direct effects of microRNAs and proteins encapsulated in EVs and indirect paracrine effects on M2 macrophages.CONCLUSIONS:
Clinical-grade iPSCM-derived EVs improve cardiac function by regulating various genes and pathways in various cell types and may have clinical potential for treating ischemic heart disease.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
MicroRNAs
/
Células-Tronco Pluripotentes Induzidas
/
Vesículas Extracelulares
/
Cardiomiopatias
/
Infarto do Miocárdio
Limite:
Animals
Idioma:
En
Revista:
J Heart Lung Transplant
Assunto da revista:
CARDIOLOGIA
/
TRANSPLANTE
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Japão